This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this study is to explore the mechanisms of virus control and immune protection in SIVmac-infected long term nonprogressors (LTNP) rhesus macaques of Chinese-origin (Ch Rh). This will be done by a combination of retrospective analysis of archived samples as well as prospective study on 7 SIVmac239-infected Ch Rh. We hypothesize that the breadth, magnitude and specificity of the immune responses will distinguish progressors and LTNP. The knowledge obtained from Ch Rh LTNP may provide implications to design more efficacious vaccines or novel therapeutic approaches to combat HIV-1 infection. The specific aims are: SA 1): To compare functional virus-specific and innate immune responses in both mucosal and systemic lymphoid tissues of SIV-infected progressing, and LTNP Ch Rh macaques. SA 2): To examine and compare gene regulation in mucosal and systemic lymphoid tissues of progressing and LTNP Ch Rh macaques infected with SIV. SA 3): To examine virologic factors in LTNP and progressors.